Administration of endogenous opiate peptides alters release of all anterior pituitary hormones. The opiate antagonists given alone produce responses opposite to the agonist. These data suggest endogenous opiates may regulate pituitary secretions. The proposed research intends to determine their involvement during physiological conditions and their significance in anterior pituitary secretion. The pattern of hormone release during environmental adaptation and reproductive processes will be compared between control rats and rats in which stimulation of the opiate receptor is prevented. Total blockade of the receptor is produced by administration of nathexone. Resulting data will indicate those conditions during which opiates induce hormone release. The response to endogenous opiates in situ can be modulated by induction of tolerance. This phenomenon will be characterized to distinguish its acute and chronic components. The effect of each type on the release of hormones during adaptation and reproduction will be examined to determine their significance and possible role as a physiological regulatory mechanism. Finally the type of opiate receptors involved in hormone release will be examined and compared with those mediating analgesia, thermoregulation and catalepsy. Preliminary indications suggest differences exist. The procedure involved is similar to Kosterlitz's and consists of ranking the potency of agonists and antagonists for several responses. Multiple receptors are indicated when rank order amongst responses differs. Both physiological responses, (hormone release, analgesia, catalepsy and thermoregulation) as well as binding of radiolabeled ligands will be considered. Data resulting from all of the above studies should indicate the relationship between endogenous opiates and anterior pituitary functions.